Multifunctional protein that plays a central role in thecellular response to oxidative stress. The two major activities ofAPEX1 are DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in theDNA base excision repair (BER) pathway of DNA lesions induced byoxidative and alkylating agents. Initiates repair of AP sites in DNA bycatalyzing hydrolytic incision of the phosphodiester backboneimmediately adjacent to the damage, generating a single-strand breakwith 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise atAP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNAregions of R-loop structures, and single-stranded RNA molecules. Has a3'-5' exoribonuclease activity on mismatched deoxyribonucleotides atthe 3' termini of nicked or gapped DNA molecules during short-patchBER. Possesses a DNA 3' phosphodiesterase activity capable of removinglesions (such as phosphoglycolate) blocking the 3' side of DNA strandbreaks. May also play a role in the epigenetic regulation of geneexpression by participating in DNA demethylation. Acts as a loadingfactor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repairleading to cell death. Also involved in the DNA cleavage step of classswitch recombination (CSR). On the other hand, APEX1 also exertsreversible nuclear redox activity to regulate DNA binding affinity andtranscriptional activity of transcriptional factors by controlling theredox status of their DNA-binding domain, such as the FOS/JUN AP-1complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding tonegative calcium response elements (nCaREs). Together with HNRNPL orthe dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator oftranscriptional repression. Stimulates the YBX1-mediated MDR1 promoteractivity, when acetylated at Lys-6 and Lys-7, leading to drugresistance. Acts also as an endoribonuclease involved in the control ofsingle-stranded RNA metabolism. Plays a role in regulating MYC mRNAturnover by preferentially cleaving in between UA and CA dinucleotidesof the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycleprogression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA. [1-25]

MPKRGKKGAVAEDGDELRTEPEAKKSKTAAKKNDKEAAGEGPALYEDPPDQKTSPSGKPATLKICSWNVDGLRAWIKKKGLDWVKEEAPDILCLQETKCSENKLPAELQELPGLSHQYWSAPSDKEGYSGVGLLSRQCPLKVSYGIGDEEHDQEGRVIVAEFDSFVLVTAYVPNAGRGLVRLEYRQRWDEAFRKFLKGLASRKPLVLCGDLNVAHEEIDLRNPKGNKKNAGFTPQERQGFGELLQAVPLADSFRHLYPNTPYAYTFWTYMMNARSKNVGWRLDYFLLSHSLLPALCDSKIRSKALGSDHCPITLYLAL